Journal
MARINE ENVIRONMENTAL RESEARCH
Volume 66, Issue 1, Pages 75-76Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.marenvres.2008.02.027
Keywords
concentration addition; independent action; mixtures; MRP; multixenobiotic resistance; Mytilus californianus; P-gp
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Fluorescent dyes and inhibitor compounds are commonly used to detect activity of multixenobiotic resistance (MXR) efflux pumps in marine invertebrates. We here address the question whether compounds acting as specific inhibitors of certain mammalian transporters can be used in dye efflux assays to distinguish different transporter activities in gill tissue from a marine mussel. We quantified effects of PSC833, a specific inhibitor of mammalian P-gp (P-glycoprotein, ABCB1), and MK571, which blocks MRP (Multidrug resistance associated protein, ABCC) type transporters, on calcein-am efflux in gill tissue of Mytilus californianus. Calcein-am acts as a substrate of both P-gp and MRP. Effects of single compounds and mixtures were determined and combined effect models predicting independent action (IA) and concentration addition (CA) of the chemicals were applied. Effect values predicted by IA showed better correspondence with the experimentally obtained data. This indicates that the inhibitor compounds target different mechanisms of calcein-am efflux and points to P-gp and MRP activities in mussel gills. Our approach could be a simple way for identifying the efflux transporter types targeted by chemosensitizers, including environmentally relevant compounds, in native tissues from marine invertebrates. (C) 2008 Elsevier Ltd. All rights reserved.
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